Soft tissue fillers for connective and/or fatty soft tissues are used in both medical and cosmetic applications to correct various soft tissue defects or to enhance appearance. Soft tissue defects may be caused by various conditions such as soft tissue tumor resection, congenital abnormalities, trauma and aging.
Various compounds have been used as soft tissue fillers, including hyaluronic acid, collagen, as well as biosynthetic polymers, e.g., poly-L-lactic acid, calcium hydroxylapatite, and polymethylmethacrylate, in addition to implants, such as silicone-based implants or using a patients' own fat as a soft tissue filler. Non-limiting examples of various injectable dermal soft tissue fillers commercially available are. hyaluronic acid (e.g. Restylane™ and Juvéderm™); collagen (e.g. Zyderm™, Zyplast™), as well as biosynthetic polymers (e.g. Radiesse™ (calcium hydroxylapatite); Ellansé™ (Polycaprolactone); Sculptra™ (Poly-L-lactic acid). These fillers are commonly injectable. These approaches have various disadvantages. Natural materials can have problems with sourcing and control and consistency of materials. Shaped implants must be pre-sized and do not have the flexibility provided by other fillers, such as e.g. injectable fillers. The use of a patients' own tissue can further complicate surgical procedures and may be associated with higher post-operative complications. Additionally, where the soft tissue fillers are used to address medical concerns, cosmetic concerns are often not adequately addressed by these soft tissue fillers.
One area where poor cosmetic results are particularly problematic is treatment following repair of breast tissue defects arising as a result of breast cancer or the treatment thereof.
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in Canadian women. Approximately, 25,000 Canadian women were diagnosed with breast cancer in 2015 (Canadian Cancer Society), accounting for 26% of all new cancer cases. After several randomized controlled trials confirming the safety and efficacy of breast conserving surgery (BCS) with radiation, it has replaced mastectomy as the most common surgical procedure for breast cancer. Due to improved treatments, most breast cancer survivors are now expected to have a long life expectancy with a good quality of life. However, poor cosmesis and irregular soft tissue defects are commonly observed in patients that undergo BCS. While impairing the patients' aesthetic appearance, soft tissue defects are a main source of psychological distress, emphasizing the increasing need for correction/restoration techniques to address these cosmetic issues. Since commercially-available synthetic implants are fabricated in pre-determined sizes, they are not suitable to reconstruct partial breast deformities of varying sizes and are solely used for full breast reconstruction in post-mastectomy settings.
Several surgical techniques have been explored to address this unmet need. For example, there are a number of oncoplastic surgical techniques available such as local tissue rearrangement, contralateral breast reduction and flap procedures. However, high rates of complications and cost (long operative time and hospital stay) are drawbacks. Local tissue rearrangement, while demonstrating lower complications rates and more cosmetically-acceptable results, is not suitable for patients who have fatty breasts and insufficient breast tissue after resection. Furthermore, in order to achieve symmetry, up to 40% of these patients will require a contralateral breast reduction, consequently increasing the overall surgery time and complications for both breasts. Tissue rearrangement can also complicate revisions of positive surgical margins when needed. This may lead to the decision of performing a mastectomy due to the inability to ascertain the involved margins accurately. Pedicle flap procedures (e.g., latissimus dorsi flap) are recommended for patients with small breasts or significant tissue loss. Advantages of this reconstruction technique are the lack of need for contralateral breast reduction as well as the surgeon's ability to be more aggressive with breast tissue resection without cosmetic detriment. However, extensive surgical dissection, long surgery and recovery time, donor site complications, high costs as well as aesthetic limitations due to potential differences in skin color and texture are main drawbacks of flap procedures.
Autologous fat transfer has also been used to fill the breast defect after BCS. However, this technique offers a temporary solution due to cytosteatonecrosis. More recent reconstruction methods include the use of adipose-derived regenerative cell (ADRC)-enriched fat grafts (Cytori Therapeutics Inc.), platelet-rich plasma (PRP) fat grafts, PRP gels or dermal grafts (Alloderm, LifeCell Corp.), which have shown improved cosmetic outcomes. However, these techniques are in their infancy.
There remains a need for improved and/or alternate methods for partial breast reconstructions and soft tissue fillers.